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If a peripheral, behaviorally irrelevant cue is followed by a target at the same position, response time for the target is either facilitated or inhibited relative to the response at an uncued position, depending on the delay between target and cue (Posner, 1980; Posner & Cohen, 1984). A few studies have suggested that this spatial cueing effect (termed reflexive spatial attention) is affected by non-spatial cue and target attributes such as orientation or shape. We measured the dependence of the spatial cueing effect on the shapes of the cue and the target for a range of cue onset to target onset asynchronies (CTOAs). When cue and target shapes were different, the spatial cueing effect was facilitatory for short CTOAs and inhibitory for longer CTOAs. The facilitatory spatial effect at short CTOAs was substantially reduced when cue and target shapes were the same. We present a simple neural network to explain our data, providing a unified explanation for the spatial cueing effect and its dependence on shape similarities between the cue and the target. Our modeling suggests that one does not need independent mechanisms to explain both facilitatory and inhibitory spatial cueing effects. Because the neuronal properties (repetition suppression) and the network connectivity (mutual inhibition) of the model are present throughout many visual brain regions, it is possible that reflexive attentional effects may be distributed throughout the brain with different regions expressing different types of reflexive attention depending on their sensitivities to various aspects of visual stimuli. [ABSTRACT FROM AUTHOR]

Many studies have shown that the human visual system has two major functionally distinct cortical visual pathways: a ventral pathway, thought to be important for object recognition, and a dorsal pathway, thought to be important for spatial cognition. According to our and others previous studies, artificial neural networks with two segregated pathways can determine objects' identities and locations more accurately and efficiently than one-pathway artificial neural networks. In addition, we showed that these two segregated artificial cortical visual pathways can each process identity and spatial information of visual objects independently and differently. However, when using such networks to process multiple objects' identities and locations, a binding problem arises because the networks may not associate each object's identity with its location correctly. In a previous study, we constrained the binding problem by training the artificial identity pathway to retain relative location information of objects. This design uses a location map to constrain the binding problem. One limitation of that study was that we only considered two attributes of our objects (identity and location) and only one possible map (location) for binding. However, typically the brain needs to process and bind many attributes of an object, and any of these attributes could be used to constrain the binding problem. In our current study, using visual objects with multiple attributes (identity, luminance, orientation, and location) that need to be recognized, we tried to find the best map (among an identity map, a luminance map, an orientation map, or a location map) to constrain the binding problem. We found that in our experimental simulations, when visual attributes are independent of each other, a location map is always a better choice than the other kinds of maps examined for constraining the binding problem. Our findings agree with previous neurophysiological findings that show that the organization or map in many visual cortical areas is primarily retinotopic or spatial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Han and Sereno.)

Normal aging often results in an increase in physiological tremors and slowing of the movement of the hands, which can impair daily activities and quality of life. This study, using lightweight wearable non-invasive sensors, aimed to detect and identify age-related changes in wrist kinematics and response latency. Eighteen young (ages 18-20) and nine older (ages 49-57) adults performed two standard tasks with wearable inertial measurement units on their wrists. Frequency analysis revealed 5 kinematic variables distinguishing older from younger adults in a postural task, with best discrimination occurring in the 9-13 Hz range, agreeing with previously identified frequency range of age-related tremors, and achieving excellent classifier performance (0.86 AUROC score and 89% accuracy). In a second pronation-supination task, analysis of angular velocity in the roll axis identified a 71 ms delay in initiating arm movement in the older adults. This study demonstrates that an analysis of simple kinematic variables sampled at 100 Hz frequency with commercially available sensors is reliable, sensitive, and accurate at detecting age-related increases in physiological tremor and motor slowing. It remains to be seen if such sensitive methods may be accurate in distinguishing physiological tremors from tremors that occur in neurological diseases, such as Parkinson's Disease., (© 2024. The Author(s).)

The two visual cortical stream hypothesis, which suggests object properties (what) are processed separately from spatial properties (where), has a longstanding history, and much evidence has accumulated to support its conjectures. Nevertheless, in the last few decades, conflicting evidence has mounted that demands some explanation and modification. For example, existence of (1) shape activities (fMRI) or shape selectivities (physiology) in dorsal stream, similar to ventral stream; likewise, spatial activations (fMRI) or spatial selectivities (physiology) in ventral stream, similar to dorsal stream; (2) multiple segregated subpathways within a stream. In addition, the idea of segregation of various aspects of multiple objects in a scene raises questions about how these properties of multiple objects are then properly re-associated or bound back together to accurately perceive, remember, or make decisions. We will briefly review the history of the two-stream hypothesis, discuss competing accounts that challenge current thinking, and propose ideas on why the brain has segregated pathways. We will present ideas based on our own data using artificial neural networks (1) to reveal encoding differences for what and where that arise in a two-pathway neural network, (2) to show how these encoding differences can clarify previous conflicting findings, and (3) to elucidate the computational advantages of segregated pathways. Furthermore, we will discuss whether neural networks need to have multiple subpathways for different visual attributes. We will also discuss the binding problem (how to correctly associate the different attributes of each object together when there are multiple objects each with multiple attributes in a scene) and possible solutions to the binding problem. Finally, we will briefly discuss problems and limitations with existing models and potential fruitful future directions., (© 2024 Massachusetts Institute of Technology.)

Gabiroba, a native fruit in Brazil's Atlantic Forest region, has significant nutritional and therapeutic properties. However, due to its seasonality, consumption by the population is limited. Thus, the development of gabiroba byproducts would add significant value to the food and therapeutic industries. Therefore, it is essential to study and support the lack of toxicity of gabiroba fruit extracts. In the present study, physicochemical analyses of fresh fruits (GF) and dehydrated whole gabiroba flour (WGF) and preliminary toxicity analyses of WGF were performed. The toxicity results showed a microcrustacean LC50 of >1000 mg/mL when exposed to WGF extracts at various concentrations (10-1000 μg/mL; p = 0.062) using the Artemia salina method, with no evidence observed of proliferative activity or toxic metabolic compounds in the WGF extract. The phytotoxicity of WGF using Lactuca sativa L. allowed germination and root growth at various concentrations of WGF extract, with the lowest (100 μg/mL) and highest (1000 μg/mL) concentrations exhibiting 98.3% and 100% seed germination, respectively. In conclusion, these results indicate that the WGF preparation preserved the nutritional and antioxidant potential of gabiroba fruits and that WGF is safe for use as a raw material in the food industry and for therapeutic purposes.

There is growing interest in the effects of sports-related repetitive head impacts (RHIs) on athletes' cognitive capabilities. This study examines the effect of RHIs in data collected from adolescent athletes to estimate the magnitude and longevity of RHIs on sensorimotor and cognitive performance. A non-linear regression model estimated the longevity of RHI effects by adding a half-life parameter embedded in an exponential decay function. A model estimate of this parameter allows the possibility of RHI effects to attenuate over time and introduces a mechanism to study the cumulative effect of RHIs. The posterior distribution of the half-life parameter associated with short-distance headers (<30 m) is centered around 6 days, whereas the posterior distribution of the half-life parameter associated with long-distance headers extends beyond a month. Additionally, the magnitude of the effect of each short header is around 3 times smaller than that of a long header. The results indicate that, on both tasks, response time (RT) changes after long headers are bigger in magnitude and last longer compared to the effects of short headers. Most important, we demonstrate that deleterious effects of long headers extend beyond 1 month. Although estimates are based on data from a relatively short-duration study with a relatively small sample size, the proposed model provides a mechanism to estimate long-term behavioral slowing from RHIs, which may be helpful to reduce the risk of additional injury. Finally, differences in the longevity of the effects of short and long RHIs may help to explain the large variance found between biomechanical input and clinical outcome in studies of concussion tolerance., Competing Interests: A.B.S. is a named inventor of patents US-9,717,459 (August 1, 2017), US-9,949,693 (April 24, 2018), and US-10849559 (December 1, 2020). A.B.S. is an owner of CogNeuro Solutions LLC. These patents are for systems and methods to achieve accurate timing on capacitance devices such as an iPad., (© Farzin Shamloo et al., 2023; Published by Mary Ann Liebert, Inc.)

The application of β-galactosidase in the fermentation of milk enables the acquirement of lower levels of lactose that are tolerated by lactose maldigesters and can reduce the nutritional consequences of avoiding dairy products. The present study evaluated the viability of the fortification of lactose-free prebiotic Greek yogurt formulas with whey protein concentrate (WPC). Two rotational central composite designs (RCCDs) were applied: one to perform the hydrolysis of the whey protein concentrate and another for the yogurt formulations (α = 2 with 2 central points and 4 axial points). Two β-galactosidase enzymes obtained from Kluyveromyces lactis were used. The content of lactose, glucose, galactose, and lactic acid were determined in the WPC, milk (pasteurized and powdered), and yogurts. The three best formulations regarding the attributes’ viscosity, syneresis, firmness, and elasticity were sensorially evaluated by using a nine-point hedonic scale. A microbiological analysis was performed after 48 h of yogurt production. The characterization of the products and the comparison of the results obtained were evaluated using the Student’s T test and the analysis of variance with Tukey’s test (p-values < 0.05). The application of a lactose-free WPC promoted viscosity, firmness, and elasticity. The syneresis was reduced, and whey increased the protein and calcium content. Lactose-free WPC can be used as a partial substitute for skimmed powdered milk in yogurts. The obtained results are encouraging with respect to the production of lactose-free Greek yogurts by the dairy industry.

Ethnopharmacological Relevance: Okra (Abelmoschus esculentus (L.) Moench) is traditionally used by different populations of Africa, América, Asia, and Europa to control diabetes. Although its action has been evaluated in several preclinical rodent trials, they have not been systematically analyzed., Objective: To evaluate the effectiveness of using okra in the treatment of diabetes in experimental rodent models., Material and Methods: Controlled and randomized rodent animal trials with induced diabetes published between January 2000 and January 2021 were searched in the PubMed, Scopus, Scielo, and Web of Science databases. The search strategy included studies comprising the descriptors: animal species, diabetes induction method, intervention time, part of okra fruit used (whole, seeds, or peels), and dose as well as observed effects on biochemical and metabolic parameters. The systematic review was carried out according to the PRISMA statement, Cochrane bias risk tool (SYRCLE's RoB tool), and registered for systematic review protocols (PROSPERO)., Results: A total of 326 articles were identified and after the exclusion of studies with gestational animal models, non-rodent animals, and non-diabetic animals, 11 studies involving 388 rodents were selected for the synthesis of results. The diabetes induction methods included streptozotocin, streptozotocin-nicotinamide, alloxan monohydrate, insulin resistance by high-fat diets or formulation described in AIN - 76, and feeding with high-fat food. Both Wistar albino rats, Sprague-Dawley males, and rats of both sexes of the Long-Evans lineage as well as male albino mice and C57BL females were included in the experiments. Studies showed that extracts of the fruit, the fresh fruit, or its various fractions had positive effects on the following markers: glycated hemoglobin, cholesterol, HOMA-IR, oral glucose tolerance test, and blood glucose, in acute (2 and 24 h), and chronic (up to 4 months) treatment., Conclusion: An important hypoglycemic effect of okra in its various fractions on induced diabetes was observed by different authors. Moreover, okra promoted improvement in metabolic markers such as insulin sensitivity, lipid profile, and bodyweight loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

When measuring sparseness in neural populations as an indicator of efficient coding, an implicit assumption is that each stimulus activates a different random set of neurons. In other words, population responses to different stimuli are, on average, uncorrelated. Here we examine neurophysiological data from four lobes of macaque monkey cortex, including V1, V2, MT, anterior inferotemporal cortex, lateral intraparietal cortex, the frontal eye fields, and perirhinal cortex, to determine how correlated population responses are. We call the mean correlation the pseudosparseness index, because high pseudosparseness can mimic statistical properties of sparseness without being authentically sparse. In every data set we find high levels of pseudosparseness ranging from 0.59-0.98, substantially greater than the value of 0.00 for authentic sparseness. This was true for synthetic and natural stimuli, as well as for single-electrode and multielectrode data. A model indicates that a key variable producing high pseudosparseness is the standard deviation of spontaneous activity across the population. Consistently high values of pseudosparseness in the data demand reconsideration of the sparse coding literature as well as consideration of the degree to which authentic sparseness provides a useful framework for understanding neural coding in the cortex.

Research suggests cumulative effects of repetitive head impacts (RHIs) on brain structure, especially with younger age of first exposure. Further, recent evidence suggests no immediate cognitive changes with increased RHIs but impairments across a sports season. The aim was to examine more closely the short-term time course of behavioral effects of exposure to RHI. Across 2 years, 18 female adolescent soccer players were tested on ProPoint (sensorimotor) and AntiPoint (cognitive) tasks with reaction time (RT) being the main outcome measure. The athletes were tested before and after workout with ball heading (immediate effect), as well as 24 h after workout (24 h effect) throughout two consecutive seasons. The number of headers performed 24 h before workout, during workout, and season average per workout were recorded. The athletes showed a decrease in ProPoint and AntiPoint RTs immediately after a workout, with no change or decrease in RTs with increasing RHIs. However, increasing RHIs during workout increased RTs in both tasks when tested 24 h later. The athletes also showed an increase in AntiPoint RTs with increasing season average RHIs. Our findings show a complex time course of effects of RHIs on sensorimotor and cognitive performance in adolescent athletes, with exposure to RHIs associated with no change or immediate benefits and then deficits by 24 h. Pathophysiological changes associated with exercise and traumatic brain injury can account for the sensorimotor and cognitive performance changes occurring within 24 h after RHIs.

Objective: Schizophrenia patients show executive function (EF) impairments in voluntary orienting as measured by eye-movements. We tested 14 inpatients to investigate the effects of the antipsychotic olanzapine on EF, as measured by antisaccade eye-movement performance., Methods: Patients were tested at baseline (before olanzapine), 3-5 days post-medication, and 12-14 days post-medication. Patients were also assessed on the Positive and Negative Syndrome Scale (PANSS) to measure the severity of schizophrenia-related symptoms, and administered the Stroop task, a test of EF. Nine matched controls were also tested on the antisaccade and Stroop., Results: Both groups showed improvement on Stroop and antisaccade; however, the schizophrenia group improved significantly more on antisaccade, indicating an additional benefit of olanzapine on EF performance. Patients with poorer baseline antisaccade performance (High-Deficit) showed significantly greater improvement on the antisaccade task than patients with better baseline performance (Low-Deficit), suggesting that baseline EF impairment predicts the magnitude of cognitive improvement with olanzapine. These subgroups showed significant and equivalent improvement on PANSS scores, indicating that improvement on the antisaccade task with olanzapine was not a result of differences in magnitude of clinical improvement., Conclusions: This preliminary study provides evidence that olanzapine may be most advantageous for patients with greater baseline EF deficits., (© 2019 John Wiley & Sons Ltd.)

Attentional deficits are core to numerous developmental, neurological, and psychiatric disorders. At the single-cell level, much knowledge has been garnered from studies of shape and spatial properties, as well as from numerous demonstrations of attentional modulation of those properties. Despite this wealth of knowledge of single-cell responses across many brain regions, little is known about how these cellular characteristics relate to population level representations and how such representations relate to behavior; in particular, how these cellular responses relate to the representation of shape, space, and attention, and how these representations differ across cortical areas and streams. Here we will emphasize the role of population coding as a missing link for connecting single-cell properties with behavior. Using a data-driven intrinsic approach to population decoding, we show that both 'what' and 'where' cortical visual streams encode shape, space, and attention, yet demonstrate striking differences in these representations. We suggest that both pathways fully process shape and space, but that differences in representation may arise due to their differing functions and input and output constraints. Moreover, differences in the effects of attention on shape and spatial population representations in the two visual streams suggest two distinct strategies: in a ventral area, attention or task demands modulate the population representations themselves (perhaps to expand or enhance one part at the expense of other parts) while in a dorsal area, at a population representation level, attention effects are weak and nearly non-existent, perhaps in order to maintain veridical representations needed for visuomotor control. We show that an intrinsic approach, as opposed to theory-driven and labeled approaches, is useful for understanding how representations develop and differ across brain regions. Most importantly, these approaches help link cellular properties more tightly with behavior, a much-needed step to better understand and interpret cellular findings and key to providing insights to improve interventions in human disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We extend the discussion in the target article about distinctions between extrinsic coding (external references to known things, as required by information theory) and the alternative we and the target article both favor, intrinsic coding (internal relationships within sensory and motor signals). Central to our thinking about intrinsic coding is population coding and the concept of high-dimensional neural response spaces.

Changes in prefrontal cortex are thought to be responsible for many of the characteristic behavioral changes that are seen during adolescence and late adulthood. Disruption of prefrontal cortex is an early sign for many developmental, neurological, and psychiatric disorders. Goal directed eye movements, such as Anti-saccades, have been shown to have high sensitivity as a gross assessment of prefrontal lobe function. Previous studies on the developmental changes of saccades across age have shown that stimulus-driven and goal-directed eye movements follow a U -shaped trend with peaks in performance occuring during adolescence. Using novel tablet-based pointing tasks, modeled on eye movement tests, this study aims to provide a preliminary understanding of how age affects manual pointing performance, in order to more easily track behavioral changes of the prefrontal cortex. In this study, 82 participants between the ages of 10 and 63 were recruited to participate. Results show that similarly to saccades, manual pointing responses are age dependent with fastest response times found during late adolescence to early adulthood ( U -shaped curves). Importantly, we also demonstrated significant differences in the effect of age in stimulus-driven (Pro-point) and goal-directed (Anti-point) pointing tasks. The effect of age on response time (RT) is greater on Anti-point compared to Pro-point task (with a 79 ms greater mean decrease during early development and a 148 ms greater mean increase during later aging). Further, for Pro-point task, the U -shaped curve flattens at about 45 years whereas for Anti-point task the U -shaped curve continues up to the maximum age tested (about 60 years). This dissociation between age-related changes in sensorimotor and cognitive performance suggests independent development of associated brain circuity. Thus, changes of performance in disease that are specific for age and task may be able to help identify brain circuitry involved. Finally, given that these tablet-based pointing tasks show similar age-related patterns reported previously with eye-tracking technology, our findings suggest that such tablet-based tasks may provide an inexpensive, quick, and more practical way of detecting neurological deficits or tracking cognitive changes.

[This corrects the article DOI: 10.1371/journal.pone.0057364.].

We examined how attention causes neural population representations of shape and location to change in ventral stream (AIT) and dorsal stream (LIP). Monkeys performed two identical delayed-match-to-sample (DMTS) tasks, attending either to shape or location. In AIT, shapes were more discriminable when directing attention to shape rather than location, measured by an increase in mean distance between population response vectors. In LIP, attending to location rather than shape did not increase the discriminability of different stimulus locations. Even when factoring out the change in mean vector response distance, multidimensional scaling (MDS) still showed a significant task difference in AIT, but not LIP, indicating that beyond increasing discriminability, attention also causes a nonlinear warping of representation space in AIT. Despite single-cell attentional modulations in both areas, our data show that attentional modulations of population representations are weaker in LIP, likely due to a need to maintain veridical representations for visuomotor control.

Worldwide, more than 22 million children and adolescents are exposed to repetitive head impacts (RHI) in soccer. Evidence indicates cumulative effects on brain structure, but it is not known whether exposure to RHI affects cognitive improvement in adolescents. The aim of the study was to determine whether exposure to RHI while heading the ball in soccer affects improvement in cognitive performance in adolescents over time. The study group consisted of a convenience sample of 16 male soccer players (mean age 15.7 ± 0.7 years). A comparison cohort of 14 male non-contact sports athletes (mean age 14.9 ± 1.1 years) was recruited from competitive athletic clubs and group-matched in age. Using the ProPoint and AntiPoint tasks, sensorimotor and cognitive functions were measured over both immediate (pre- vs. post-training) as well as across multiple time points within a play season. The number and type of head impacts that occurred during the training were counted. The main outcome measure was the change in response time (RT) in the ProPoint and AntiPoint tasks. The immediate (pre- vs. post-training) and longer-term (across a play season) change in RT was analyzed, and the effect of the number and type of head impacts was tested. Thirty athletes with and without exposure to RHI demonstrated a decrease in RT in both tasks immediately after training. Over the play season, both groups showed improvement in sensorimotor function. While the control group also improved in cognitive performance, the soccer players did not, however. Further, the more long headers performed, the slower the improvement in RT over the season. Youth athletes experience an immediate cognitive improvement after training most likely because of physical exercise. Results of this study also suggest an association between exposure to specific RHI (long headers) and lack of improvement in cognitive performance in youth athletes over time.

Study Objective: Medical residents working overnight call shifts experience sleep deprivation and circadian clock disruption. This leads to deficits in sensorimotor function and increases in workplace accidents. Using quick tablet-based tasks, we investigate whether measureable executive function differences exist following a single overnight call versus routine shift, and whether factors like stress, rest and caffeine affect these measures., Design: A prospective, observational, longitudinal, comparison study was conducted., Setting: An academic tertiary hospital's main operating room suite staffed by attending anesthesiologists, anesthesiology residents, anesthesiologist assistants and nurse anesthetists., Patients: Subjects were 30 anesthesiology residents working daytime shifts and 30 peers working overnight call shifts from the University of Texas Health Science Center at Houston., Interventions: Before and after their respective work shifts, residents completed the Stanford Sleepiness Scale (SSS) and the ProPoint and AntiPoint tablet-based tasks. These latter tasks are designed to measure sensorimotor and executive functions, respectively., Measurements: The SSS is a self-reported measure of sleepiness. Response times (RTs) are measured in the pointing tasks., Main Results: Call residents exhibited increased RTs across their shifts (post-pre) on both ProPoint (p=0.002) and AntiPoint (p<0.002) tasks, when compared to Routine residents. Increased stress was associated with decreases in AntiPoint RT for Routine (p=0.007), but with greater increases in sleepiness for Call residents (p<0.001). Further, whether or not a Call resident consumed caffeine habitually was associated with ProPoint RT changes; with Call residents who habitually drink caffeine having a greater Pre-Post difference (i.e., more slowing, p<0.001) in ProPoint RT., Conclusions: These results indicate that (1) overnight Call residents demonstrate both sensorimotor and cognitive slowing compared to routine daytime shift residents, (2) sensorimotor slowing is greater in overnight Call residents who drink caffeine habitually, and (3) increased stress during a shift reduces (improves) cognitive RTs during routine daytime but not overnight call shifts., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD ( N  = 21), MSA ( N  = 11), and age-matched controls (C, N  = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders.

This study examined the potential for novel tablet-based tasks, modeled after eye tracking techniques, to detect subtle sensorimotor and cognitive deficits after mild traumatic brain injury (mTBI). Specifically, we examined whether performance on these tablet-based tasks (Pro-point and Anti-point) was able to correctly categorize concussed versus non-concussed participants, compared with performance on other standardized tests for concussion. Patients admitted to the emergency department with mTBI were tested on the Pro-point and Anti-point tasks, a current standard cognitive screening test (i.e., the Standard Assessment of Concussion [SAC]), and another eye movement-based tablet test, the King-Devick(®) (KD). Within hours after injury, mTBI patients showed significant slowing in response times, compared with both orthopedic and age-matched control groups, in the Pro-point task, demonstrating deficits in sensorimotor function. Mild TBI patients also showed significant slowing, compared with both control groups, on the Anti-point task, even when controlling for sensorimotor slowing, indicating deficits in cognitive function. Performance on the SAC test revealed similar deficits of cognitive function in the mTBI group, compared with the age-matched control group; however, the KD test showed no evidence of cognitive slowing in mTBI patients, compared with either control group. Further, measuring the sensitivity and specificity of these tasks to accurately predict mTBI with receiver operating characteristic analysis indicated that the Anti-point and Pro-point tasks reached excellent levels of accuracy and fared better than current standardized tools for assessment of concussion. Our findings suggest that these rapid tablet-based tasks are able to reliably detect and measure functional impairment in cognitive and sensorimotor control within hours after mTBI. These tasks may provide a more sensitive diagnostic measure for functional deficits that could prove key to earlier detection of concussion, evaluation of interventions, or even prediction of persistent symptoms.

We have previously demonstrated differences in eye-position spatial maps for anterior inferotemporal cortex (AIT) in the ventral stream and lateral intraparietal cortex (LIP) in the dorsal stream, based on population decoding of gaze angle modulations of neural visual responses (i.e., eye-position gain fields). Here we explore the basis of such spatial encoding differences through modeling of gain field characteristics. We created a population of model neurons, each having a different eye-position gain field. This population was used to reconstruct eye-position visual space using multidimensional scaling. As gain field shapes have never been well-established experimentally, we examined different functions, including planar, sigmoidal, elliptical, hyperbolic, and mixtures of those functions. All functions successfully recovered positions, indicating weak constraints on allowable gain field shapes. We then used a genetic algorithm to modify the characteristics of model gain field populations until the recovered spatial maps closely matched those derived from monkey neurophysiological data in AIT and LIP. The primary differences found between model AIT and LIP gain fields were that AIT gain fields were more foveally dominated. That is, gain fields in AIT operated on smaller spatial scales and smaller dispersions than in LIP. Thus, we show that the geometry of eye-position visual space depends on the population characteristics of gain fields, and that differences in gain field characteristics for different cortical areas may underlie differences in the representation of space.

Impairment in social interactions is a primary characteristic of people diagnosed with autism spectrum disorder (ASD). Although these individuals tend to orient less to naturalistic social cues than do typically developing (TD) individuals, laboratory experiments testing social orienting in ASD have been inconclusive, possibly because of a failure to fully isolate reflexive (stimulus-driven) and voluntary (goal-directed) social orienting processes. The purpose of the present study was to separately examine potential reflexive and/or voluntary social orienting differences in individuals with ASD relative to TD controls. Subjects (ages 7-14) with high-functioning ASD and a matched control group completed three gaze cueing tasks on an iPad in which individuals briefly saw a face with averted gaze followed by a target after a variable delay. Two tasks were 100% predictive with either all congruent (target appears in gaze direction) or all incongruent (target appears opposite from gaze direction) trials, respectively. Another task was non-predictive with these same trials (half congruent and half incongruent) intermixed randomly. Response times (RTs) to the target were used to calculate reflexive (incongruent condition RT-congruent condition RT) and voluntary (non-predictive condition RT-predictive condition RT) gaze cueing effects. Subjects also completed two additional non-social orienting tasks (ProPoint and AntiPoint). Subjects with ASD demonstrate intact reflexive but deficient voluntary gaze following. Similar results were found in a separate test of non-social orienting. This suggests problems with using social cues, but only in a goal-directed fashion, in our sample of high-functioning individuals with ASD. Such findings may not only explain inconclusive previous findings but more importantly be critical for understanding social dysfunctions in ASD and for developing future interventions.

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey's task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes.

Cocaine-dependent (CD) subjects show attentional bias toward cocaine-related cues, and this form of cue-reactivity may be predictive of craving and relapse. Attentional bias has previously been assessed by models that present drug-relevant stimuli and measure physiological and behavioral reactivity (often reaction time). Studies of several CNS diseases outside of substance use disorders consistently report anti-saccade deficits, suggesting a compromise in the interplay between higher-order cortical processes in voluntary eye control (i.e., anti-saccades) and reflexive saccades driven more by involuntary midbrain perceptual input (i.e., pro-saccades). Here, we describe a novel attentional-bias task developed by using measurements of saccadic eye movements in the presence of cocaine-specific stimuli, combining previously unique research domains to capitalize on their respective experimental and conceptual strengths. CD subjects (N = 46) and healthy controls (N = 41) were tested on blocks of pro-saccade and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Analyses of eye-movement data indicated (1) greater overall anti-saccade errors in the CD group; (2) greater attentional bias in CD subjects as measured by anti-saccade errors to cocaine-specific (relative to neutral) stimuli; and (3) no differences in pro-saccade error rates. Attentional bias was correlated with scores on the obsessive-compulsive cocaine scale. The results demonstrate increased saliency and differential attentional to cocaine cues by the CD group. The assay provides a sensitive index of saccadic (visual inhibitory) control, a specific index of attentional bias to drug-relevant cues, and preliminary insight into the visual circuitry that may contribute to drug-specific cue reactivity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Reports conflict as to whether Tourette syndrome (TS) confers deficits in executive function. This study's aim was to evaluate executive function in youths with TS using oculomotor tasks while controlling for confounds of tic severity, age, medication, and severity of comorbid disorders., Method: Four saccade tasks requiring the executive functions of response generation, response inhibition, and working memory (prosaccade, antisaccade, 0-back, and 1-back) were administered. Twenty youths with TS and low tic severity (TS-low), nineteen with TS and moderate tic severity (TS-moderate), and 29 typically developing control subjects (Controls) completed the oculomotor tasks., Results: There were small differences across groups in the prosaccade task. Controlling for any small sensorimotor differences, TS-moderate subjects had significantly higher error rates than Controls and TS-low subjects in the 0-back and 1-back tasks. In the 1-back task, these patients also took longer to respond than Controls or TS-low subjects., Conclusions: In a highly controlled design, the findings demonstrate for the first time that increased tic severity in TS is associated with impaired response inhibition and impaired working memory and that these executive function deficits cannot be accounted for by differences in age, medication or comorbid symptom severity., (© 2014 Association for Child and Adolescent Mental Health.)

We recorded visual responses while monkeys fixated the same target at different gaze angles, both dorsally (lateral intraparietal cortex, LIP) and ventrally (anterior inferotemporal cortex, AIT). While eye-position modulations occurred in both areas, they were both more frequent and stronger in LIP neurons. We used an intrinsic population decoding technique, multidimensional scaling (MDS), to recover eye positions, equivalent to recovering fixated target locations. We report that eye-position based visual space in LIP was more accurate (i.e., metric). Nevertheless, the AIT spatial representation remained largely topologically correct, perhaps indicative of a categorical spatial representation (i.e., a qualitative description such as "left of" or "above" as opposed to a quantitative, metrically precise description). Additionally, we developed a simple neural model of eye position signals and illustrate that differences in single cell characteristics can influence the ability to recover target position in a population of cells. We demonstrate for the first time that the ventral stream contains sufficient information for constructing an eye-position based spatial representation. Furthermore we demonstrate, in dorsal and ventral streams as well as modeling, that target locations can be extracted directly from eye position signals in cortical visual responses without computing coordinate transforms of visual space.

The target article does not consider neural data on primate spatial representations, which we suggest provide grounds for believing that navigational space may be three-dimensional rather than quasi-two-dimensional. Furthermore, we question the authors' interpretation of rat neurophysiological data as indicating that the vertical dimension may be encoded in a neural structure separate from the two horizontal dimensions.

Current population coding methods, including weighted averaging and Bayesian estimation, are based on extrinsic representations. These require that neurons be labeled with response parameters, such as tuning curve peaks or noise distributions, which are tied to some external, world-based metric scale. Firing rates alone, without this external labeling, are insufficient to represent a variable. However, the extrinsic approach does not explain how such neural labeling is implemented. A radically different and perhaps more physiological approach is based on intrinsic representations, which have access only to firing rates. Because neurons are unlabeled, intrinsic coding represents relative, rather than absolute, values of a variable. We show that intrinsic coding has representational advantages, including invariance, categorization, and discrimination, and in certain situations it may also recover absolute stimulus values.

Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction.

A pilot feasibility study was conducted to determine whether Directly Observed Therapy Short-Course (DOTS) workers could be trained to deliver smoking cessation counseling and referral interventions, identify potential barriers to a full-scale randomized controlled trial on the effectiveness of integrated smoking cessation in DOTS, and determine whether tuberculosis (TB) patients who smoke would agree to participate in such a program. DOTS providers in two Rio de Janeiro primary health clinics received 1-day training in cessation counseling. They completed pre- and post-training surveys and participated in post-program focus groups. Patients were surveyed 3 months after program completion, and semiquantitative urine assays for cotinine were used to confirm cessation. Providers' mean self-efficacy scores for cessation counseling improved significantly (advise to quit, assess readiness, assist with quitting, and arrange follow-up) from scores (on a scale of 1-5) of 2-3 pre-training to 3-4 post-training (P < 0.05), with only ability to change motivation not significant. Providers' knowledge about cessation (withdrawal, nicotine replacement therapy, precontemplation) was low before training and did not improve after training (P > 0.1 for all comparisons). Implementation of a smoking cessation intervention by DOTS providers in TB clinics in Brazil is feasible. Randomized controlled trials to test intervention effectiveness in reducing TB-related morbidity must include cross-training for tobacco control and TB providers. Smoking cessation in DOTS programs may be important in reducing the global burden of TB, improving the health of TB patients, and reducing TB transmission in households.

Background: Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD., Methods: Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters., Results: Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account., Conclusions: The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In a modified reflexive spatial attention paradigm, when the cue and the target are at the same spatial location, processing of the target is faster when the cue and the target have different shapes compared to same (shape effect). Recent physiological findings suggest distinct population level encoding of shape in ventral versus dorsal cortical visual streams in monkeys. In human observers, we tested whether the effect of shape on reflexive spatial attention could be attributed to ventral and/or dorsal stream encoding of shape. In the modified reflexive spatial attention paradigm, we varied the shapes of the cue and target. Based on data from monkey physiology (Lehky & Sereno, 2007), we selected four pairs of cue and target shapes. In some pairs, cue and target were similarly encoded (similar encoding distance) by a population of cells in the lateral intraparietal cortex, a dorsal stream area, but more dissimilarly encoded (having a greater encoding distance) by a population of cells in the anterior inferotemporal cortex (AIT), a ventral stream area. In other pairs, cue and target were similarly encoded in AIT and had greater dissimilarity in LIP encoding. We found that pairs of cue and target with greater dissimilarity in LIP encoding produced larger and more consistent shape effects up to a cue to target onset asynchrony (CTOA) of 450 ms. The shape effects for cue and target pairs with greater dissimilarity in AIT encoding were smaller and inconsistent, suggesting that shape effects in reflexive spatial attention are largely driven by the dorsal stream., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Valproic acid (VPA) has been suggested as a potential adjunct therapy in schizophrenia for the treatment of clinical symptoms and cognitive deficits. Here, we investigate the effects of VPA on clinical symptoms and saccadic eye movements while controlling for multiple medication effects., Methods: Remitted and first-episode schizophrenia patients taking haloperidol were given adjunct VPA for approximately 2 weeks and tested using a measure of clinical symptoms (Positive and Negative Syndrome Scale) and saccadic eye movement tasks over three testing periods. The effects of VPA were compared with schizophrenia patients medicated with equivalent doses of haloperidol alone (HAL group) and normal controls., Results: Schizophrenia patients had higher error rates on the antisaccade task (AS task) compared with normal controls. Adjunct VPA did not affect AS task error rates but was associated with an increase in response times for both saccade and AS tasks, with a significantly greater and dose-dependent increase in response times for the AS task. There were no differences in clinical improvement between VPA and HAL schizophrenia patient groups when controlling for haloperidol medication state., Conclusions: These results suggest that adjuvant VPA therapy results in both sensorimotor and cognitive slowing but does not either help or further impair inhibitory control in schizophrenia, as measured by the elevated AS task errors., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose/objectives: To examine relationships between coping resources and self-rated health among Latina breast cancer survivors., Design: Cross-sectional telephone survey., Setting: Four northern California counties., Sample: 330 Latina breast cancer survivors within one to five years of diagnosis., Methods: Telephone survey conducted by bilingual and bicultural interviewers., Main Research Variables: Predictors were sociodemographic and clinical factors, cancer self-efficacy, spirituality, and social support from family, friends, and oncologists. Outcomes were functional limitations and self-rated health., Findings: Twenty-two percent of women reported functional limitations (n = 73) and 27% reported poor or fair self-rated health (n = 89). Unemployment (adjusted odds ratio [AOR] = 7.06; 95% confidence interval [CI] [2.04, 24.46]), mastectomy (AOR = 2.67; 95% CI [1.06, 6.77]), and comorbidity (AOR = 4.09; 95% CI [1.69, 9.89]) were associated with higher risk of functional limitations; cancer self-efficacy had a protective effect (AOR = 0.4, 95% CI [0.18, 0.9]). Comorbidity was associated with higher risk of poor or fair self-rated health (AOR = 4.95; 95% CI [2.13, 11.47]); cancer self-efficacy had a protective effect (AOR = 0.3; 95% CI [0.13, 0.66])., Conclusions: Comorbidities place Latina breast cancer survivors at increased risk for poor health. Cancer self-efficacy deserves more attention as a potentially modifiable protective factor., Implications for Nursing: Nurses need to assess the impact of comorbidity on functioning and can reinforce patients' sense of control over cancer and clinician support.

We created a novel eye movement version of the n-back task to measure spatial working memory (WM). Rather than one continuous trial, discrete trials were presented in order to develop a simpler WM task. In Experiment 1, we varied the visibility of the final stimulus to maximize the difference in performance between 0-back and 1-back tasks (WM effect). In Experiment 2, we administered the optimized task to children. In Experiment 3, we further simplified the task. Both adults and children easily completed our task, displaying significant WM effects. Further, similar WM effects were obtained in our original and simplified n-back spatial WM tasks, demonstrating flexibility. Because WM deficits are often an early feature of disease and a marker of disease progression, our saccadic measure of spatial WM may be particularly useful in hard-to-test populations, such as patients and children, and may have application in brain-imaging studies that require discrete trials.

Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although the representation of space is as fundamental to visual processing as the representation of shape, it has received relatively little attention from neurophysiological investigations. In this study we characterize representations of space within visual cortex, and examine how they differ in a first direct comparison between dorsal and ventral subdivisions of the visual pathways. Neural activities were recorded in anterior inferotemporal cortex (AIT) and lateral intraparietal cortex (LIP) of awake behaving monkeys, structures associated with the ventral and dorsal visual pathways respectively, as a stimulus was presented at different locations within the visual field. In spatially selective cells, we find greater modulation of cell responses in LIP with changes in stimulus position. Further, using a novel population-based statistical approach (namely, multidimensional scaling), we recover the spatial map implicit within activities of neural populations, allowing us to quantitatively compare the geometry of neural space with physical space. We show that a population of spatially selective LIP neurons, despite having large receptive fields, is able to almost perfectly reconstruct stimulus locations within a low-dimensional representation. In contrast, a population of AIT neurons, despite each cell being spatially selective, provide less accurate low-dimensional reconstructions of stimulus locations. They produce instead only a topologically (categorically) correct rendition of space, which nevertheless might be critical for object and scene recognition. Furthermore, we found that the spatial representation recovered from population activity shows greater translation invariance in LIP than in AIT. We suggest that LIP spatial representations may be dimensionally isomorphic with 3D physical space, while in AIT spatial representations may reflect a more categorical representation of space (e.g., "next to" or "above").

We examine how the representation of space is affected by receptive field (RF) characteristics of the encoding population. Spatial responses were defined by overlapping Gaussian RFs. These responses were analyzed using multidimensional scaling to extract the representation of global space implicit in population activity. Spatial representations were based purely on firing rates, which were not labeled with RF characteristics (tuning curve peak location, for example), differentiating this approach from many other population coding models. Because responses were unlabeled, this model represents space using intrinsic coding, extracting relative positions amongst stimuli, rather than extrinsic coding where known RF characteristics provide a reference frame for extracting absolute positions. Two parameters were particularly important: RF diameter and RF dispersion, where dispersion indicates how broadly RF centers are spread out from the fovea. For large RFs, the model was able to form metrically accurate representations of physical space on low-dimensional manifolds embedded within the high-dimensional neural population response space, suggesting that in some cases the neural representation of space may be dimensionally isomorphic with 3D physical space. Smaller RF sizes degraded and distorted the spatial representation, with the smallest RF sizes (present in early visual areas) being unable to recover even a topologically consistent rendition of space on low-dimensional manifolds. Finally, although positional invariance of stimulus responses has long been associated with large RFs in object recognition models, we found RF dispersion rather than RF diameter to be the critical parameter. In fact, at a population level, the modeling suggests that higher ventral stream areas with highly restricted RF dispersion would be unable to achieve positionally-invariant representations beyond this narrow region around fixation.

Many studies have shown that the direction of gaze of a face covertly facilitates the response to a target presented in the matching direction. In this study we seek to determine whether there exist separate reflexive and voluntary forms of such covert social orienting and how they interact with each other. We measured the effect of the predictive value of a gaze cue on manual choice reaction times. When the predictive value of the gaze cue was zero, a facilitatory cueing effect was still observed which peaked at a cue onset to target onset delay (CTD) of 150ms and largely diminished beyond a CTD of 500ms. When the gaze cue was 100% predictive of the future location of the target, at CTDs greater than 200, the predictive cue resulted in a significantly greater facilitation of response than occurred with a non-predictive cue. These results suggest that given enough time (about 200ms), the social cue is interpreted and a willful or voluntary spatially-specific social cueing effect occurs. In addition, we found that a predictive cue resulted in a significant slowing of the observer's responses up to a CTD of 200ms. These findings show that, similar to non-social spatial orienting, there appear to be two forms of social orienting including a reflexive component and voluntary component. We suggest a model of social orienting in which the voluntary social orienting system modulates tonic inhibition of the reflexive social orienting system., (Published by Elsevier Ltd.)

Eye tracking dysfunction (ETD) is one of the most widely replicated behavioral deficits in schizophrenia and is over-represented in clinically unaffected first-degree relatives of schizophrenia patients. Here, we provide an overview of research relevant to the characterization and pathophysiology of this impairment. Deficits are most robust in the maintenance phase of pursuit, particularly during the tracking of predictable target movement. Impairments are also found in pursuit initiation and correlate with performance on tests of motion processing, implicating early sensory processing of motion signals. Taken together, the evidence suggests that ETD involves higher-order structures, including the frontal eye fields, which adjust the gain of the pursuit response to visual and anticipated target movement, as well as early parts of the pursuit pathway, including motion areas (the middle temporal area and the adjacent medial superior temporal area). Broader application of localizing behavioral paradigms in patient and family studies would be advantageous for refining the eye tracking phenotype for genetic studies.

Previous neurophysiological studies of the frontal eye field (FEF) in monkeys have focused on its role in saccade target selection and gaze shift control. It has been argued that FEF neurons indicate the locations of behaviorally significant visual stimuli and are not inherently sensitive to specific features of the visual stimuli per se. Here, for the first time, we directly examined single cell responses to simple, two-dimensional shapes and found that shape selectivity exists in a substantial number of FEF cells during a passive fixation task or during the sample, delay (memory), and eye movement periods in a delayed match to sample (DMTS) task. Our data demonstrate that FEF neurons show sensory and mnemonic selectivity for stimulus shape features whether or not they are behaviorally significant for the task at hand. We also investigated the extent and localization of activation in the FEF using a variety of shape stimuli defined by static or dynamic cues employing functional magentic resonance imaging (fMRI) in anesthetized and paralyzed monkeys. Our fMRI results support the electrophysiological findings by showing significant FEF activation for a variety of shape stimuli and cues in the absence of attentional and motor processing. This shape selectivity in FEF is comparable to previous reports in the ventral pathway, inviting a reconsideration of the functional organization of the visual system.

Background: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information., Methodology/principal Findings: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of recorded neurons with small gaze angle shifts from central fixation. Although eye position modulates responses, it does not change shape selectivity., Conclusions/significance: These data demonstrate that spatial information is available in AIT for the representation of objects and scenes within a non-retinocentric frame of reference. More generally, the availability of spatial information in AIT calls into questions the classic dichotomy in visual processing that associates object shape processing with ventral structures such as AIT but places spatial processing in a separate anatomical stream projecting to dorsal structures.

Background: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making., Methods: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls., Results: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades., Conclusions: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.

Ventral and dorsal visual pathways perform fundamentally different functions. The former is involved in object recognition, whereas the latter carries out spatial localization of stimuli and visual guidance of motor actions. Despite the association of the dorsal pathway with spatial vision, recent studies have reported shape selectivity in the dorsal stream. We compared shape encoding in anterior inferotemporal cortex (AIT), a high-level ventral area, with that in lateral intraparietal cortex (LIP), a high-level dorsal area, during a fixation task. We found shape selectivities of individual neurons to be greater in anterior inferotemporal cortex than in lateral intraparietal cortex. At the neural population level, responses to different shapes were more dissimilar in AIT than LIP. Both observations suggest a greater capacity in AIT for making finer shape distinctions. Multivariate analyses of AIT data grouped together similar shapes based on neural population responses, whereas such grouping was indistinct in LIP. Thus in a first comparison of shape response properties in late stages of the two visual pathways, we report that AIT exhibits greater capability than LIP for both object discrimination and generalization. These differences in the two visual pathways provide the first neurophysiological evidence that shape encoding in the dorsal pathway is distinct from and not a mere duplication of that formed in the ventral pathway. In addition to shape selectivity, we observed stimulus-driven cognitive effects in both areas. Stimulus repetition suppression in LIP was similar to the well-known repetition suppression in AIT and may be associated with the "inhibition of return" memory effect observed during reflexive attention.

Two explanations for inhibition of return (IOR) have been proposed. The first is that IOR reflects inhibition of attentional processing at previously cued locations, resulting in altered sensory analysis. The second is that IOR reflects the inhibition of responses directed towards those previously cued locations. We used a variant of a double-saccade paradigm to dissociate these two proposed effects of IOR and attempted to reveal both effects within the context of a single experimental task. Subjects viewed a series of exogenous cues and then made a localization response to subsequent targets with either a target-directed saccade or a pointing response. Results were similar for both response modes. An important finding was that the pattern of IOR depended critically on how subjects reacted to the exogenous cues. Subjects either oriented to the cued locations (via saccades or pointing) prior to responding to the target (Respond), or passively viewed the cues before responding (Ignore). In the Respond condition, IOR was observed at the most recently cued position. Although this could be consistent with an altered sensory interpretation, it would also be consistent with a spatiotopic representation. In the Ignore condition, the sole inhibited location was not the most recently cued position, but the first cued position. This finding is surprising and in conflict with previous work with multiple exogenous cues. The data are discussed in relation to a number of prominent issues in the area of IOR and suggest important new constraints and boundary conditions.

When a monkey attends to, remembers, and looks toward targets, the activity of some neurons in the lateral intraparietal area (LIP) changes. We recorded from isolated neurons during both a spatial and a shape match-to-sample task to examine and characterize voluntary active processes in LIP. Many LIP neurons show spatially selective activity during the delay period that depends on the location of the sample, but for most cells, this activity does not differ between the two tasks. Although much past work in posterior parietal cortex has explained responses in this region in terms of active processes such as decision-making and motor planning, our findings suggest that much of that activity represents more passive processing. Nevertheless, we do see a significant minority of units that demonstrate instruction-dependent activity during the delay period, suggesting that these units could represent the neural correlates of voluntary or active processes. Separately, we found that during the presentation of the sample stimulus and test array, some units show stronger responses to the stimulus in the shape-matching task when the animal must attend to the shape of a stimulus. This elevated response to the sample during the shape task provides evidence for feature-based attention in LIP. Attention to shape is a property that has not previously been described in primate cortex.

In an attempt to distinguish and define the altered cognitive processes associated with Parkinson's disease (PD), we examine and try to dissociate the components of an effective voluntary saccade: (1) the planning and execution of a voluntary saccade; (2) the suppression of reflexive eye movements; and (3) the working memory processes required. We tested 14 PD patients (off their medications) and 11 control subjects on antisaccade (AS), delayed antisaccade (DAS), and remembered antisaccade (RAS) paradigms. The three tasks required identical responses, each task only differing in a single manipulation for direct comparison--a delay period was added in the DAS, and the target was removed during the delay period of the RAS--allowing us to study the specific cognitive processes involved in the execution of a voluntary saccade. Voluntary saccade response times were longer in the PD group compared to controls on all three tasks, suggesting difficulties in voluntary saccade execution. Furthermore, PD patients showed difficulty suppressing reflexive saccades (increased number of errors in the AS task and increased number of disinhibitions in the DAS task). Finally, our study did not show significant differences in either response time or error rate between the RAS and the DAS tasks for either control subjects or PD patients. In sum, we report evidence for voluntary saccade execution deficits together with problems inhibiting reflexive saccades in Parkinson's disease patients. These findings were correlated with each other and disease severity, suggesting that eye movement measurement may be a useful tool for studying higher cognitive function.

The superior colliculus (SC) plays a central role in the control of saccadic eye movements and has also been implicated in control of covert spatial attention. While there is a growing body of evidence from studies of awake behaving primates that supports these proposals, direct evidence from humans has been sparse. In the present study we tested a patient with thiamine deficiency and a lesion of the SC, who performed both eye movement tasks (prosaccades and antisaccades, with or without a gap) and a covert spatial attention task assessing inhibition of return (IOR). For eye movements, the gap effect was disrupted, and abnormal saccade metrics occurred, with reflexive eye movements being disrupted moreso than voluntary eye movements. Each of these effects resolved coincident with thiamine treatment. The covert attention task revealed a complete absence of IOR. The unequal disruption of voluntary and reflexive eye movements supports the idea that oculomotor responses can be generated in an independent fashion by frontal cortical and lower level neural systems. The role of the SC and other structures in these orienting processes is discussed.

A polymerase chain reaction (PCR) protocol for the rapid detection of meningococcal DNA in cerebrospinal fluid (CSF) was developed and optimized. A set of primers based on Neisseria surface protein A (nspA) gene sequence was designed to amplify a 481-bp product specific for N. meningitidis. We tested 85 N. meningitidis strains obtained from patients with meningococcal meningitis and 112 CSF samples from patients with suspected meningococcal meningitis. No amplification of the nspA gene was observed from other Neisseriaceae species (except from N. gonorrhoeae) and from other bacteria frequently associated with meningitis. N. meningitidis belonging to different serogroups yielded the same product after PCR amplification. The sensitivity and specificity of our protocol was determined by comparing the results of specific amplification of nspA gene by PCR reaction (nspA-PCR) with those obtained by conventional methods. All positive samples by conventional methods were confirmed by nspA-PCR, whereas 48% of negative samples after culture and latex agglutination tested positive by nspA-PCR. The use of nspA-PCR proved to be a rapid diagnostic method, in which sensitivity and specificity may not be affected by prior antibiotic treatment.